Young Su Park

Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years

Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.

Mo1550 Prevalence and Clinicopathologic Characteristics of Gastric Cardia Cancer in South Korea

G A A b st ra ct s as H. pylori status (74.0% H. pylori positive). Pairwise linked comparison of gene expression at the different sample sites did not reveal any difference of RACGAP1 gene expression between tumor, tumor adjacent and tumor-free distant mucosa (see table 1). For biopsy samples obtained from tumor tissue there was a positive correlation of gene expression of RACGAP1 with gene expression of both β-catenin and DKK2 (β-catenin: r=0.300; p=0.036; DKK2: r=0.373; p=0.008). This could be confirmed for intestinal type not for diffuse type GC (intestinal type: β-catenin: r=0.393; p=0.039; DKK2: r=0.401; p=0.035). There was also a positive correlation of gene expression of RACGAP1 and β-catenin in samples obtained from tumor adjacent tissue (r=0.463; p=0.001), which could be confirmed for both histological types (intestinal: r=0.388; p=0.038; diffuse: r=0.622; p=0.010). Conclusion: RACGAP1 is expressed in gastric adenocarcinoma. The positive correlation of RACGAP1 with β-catenin and DKK2 suggests a functional role as modulator of Wnt-dependent signaling in intestinal type gastric cancer. Gene expression of RACGAP1, β-catenin and DKK2 (mean +/SD in arbitrary units [a.u.])

570 In Vivo PTPN2-Deficiency and a Dominant-Negative PTPN2 Mutation Cause Increased Intestinal Permeability and Alter Tight Junction Composition

We have previously generated C57BL/6J-Tg(Car1-cre)5Flt transgenic mice (CAC) with large intestine, epithelial cell-specific expression of Cre recombinase and demonstrated that they can be used to study colorectal cancer. Here we report a novel observation with CAC mice that expands their utility as an experimental model for colitis and inflammation-induced colon cancer research. CAC mice were crossed to ROSA26R reporter mice (ROSA) that have a lox-STOP-lox site controlling β-galactosidase (β-gal) expression. In study 1, 8-wk-old CAC;ROSA mice were treated with 0, 0.65, 1.35, or 2% DSS in drinking water for 5 d. Proximal (CoP) and distal colon (CoD) segments were harvest 10 d after ending DSS treatment. The colon was fixed in 10% neutral buffered formalin, paraffin embedded, and processed for determination of an epithelial damage score (reflecting % surface ulceration and% regenerating epithelium) and for immunohistochemical detection of β-gal (an indicator of Cre-mediated recombination). In control mice (0% DSS) β-gal staining was superficial in CoP while 3% of CoD epithelium had β-gal staining from crypt base to luminal surface. DSS treatment caused a dose-dependent increase in damage score for the CoP (0% DSS = 0, 0.65%DSS = 30.5±4.3, 1.35% DSS = 53.6±4.1, 2% DSS = 58.5±4.9%) and CoD epithelium (0, 24.7±8.0, 46.7±9.8, 48.4±10.6%) and this was associated with increased β-gal staining (CoP = 0.7±0.2, 20.4±1.8, 41.0±2.9, 45.9±4.6%; CoD = 3.0±0.54, 20.4±5.2, 35.4±6.9, 42.2±9.4%). Interestingly, 60% regenerating epithelium was β-gal positive regardless of the DSS dose or the colon segment examined; this new staining was seen from crypt base to luminal surface in both CoP and CoD. In study 2, we examined whether β-gal induction persisted after the epithelium had healed, reflecting Cre mediated recombination in intestinal stem cells. 8-wk-old CAC;ROSA mice were treated with 1.35% DSS and β-gal staining was assessed in colon at 10 and 30 d post DSS treatment. Epithelial β-gal staining was low in the control (CoP = 0.8±0.2%; CoD = 6.6±0.8%) and increased with the epithelial damage score at 10 d (CoP damage = 18.7±3.4%, β-gal = 17.4±2.9%; CoD damage = 27.6±7.3%, β-gal = 33.6±6.8%). At 30 d, all ulcers had healed and the % regenerating epithelium was reduced by >45% in each segment compared to the 10 d timepoint. However, epithelial βgal staining remained high in both colon segments (CoP = 18.9±1.8%; CoD = 44.4±5.2%), especially in the epithelium of the healed ulcer (CoP=75.2±4.4%; CoD = 89.4±2.2%). These studies show that in CAC mice, DSS-mediated epithelial damage can be used to induce a persistent, Cre-mediated recombination of floxed alleles. This will permit examination of the function of genes in colon epithelium during experimental colitis and inflammationinduced colon cancer.

Su1969 Comparison of H. pylori Infection, Clinicopathologic Findings and Molecular Pathology Between Young and Old Gastric Cancer Patients

lower 65 (30.1%); Period II: upper 37 (20.0%), middle 85 (45.9%), lower 61 (33.0%), Period III: upper 35 (22.2%), middle (40.5%), lower 55 (35.9%). Pathological examination revealed as follows (differentiated type/ undifferentiated/ others/ unknown); Period I: 132/ 69/0/17; Period II: 123/54/2/6; Period III: 103/43/2/0. These data indicated the locations and pathological features of the stomach cancer in this survey were not changed in recent 10 years. Regarding therapeutic approach to gastric cancer, open laparotomy was mainly applied to the gastric cancer in period I (2002-2004) as 159 out of 216 (73.6%) patients. Endoscopic treatment was performed in 38 patients (17.6%), whereas only 4 patients (1.9%) were treated under laparoscopy. In Period II (2005-2007), the ratio endoscopic treatment increased significantly (24.3%, 45/153). The ratio of laparoscopic surgery increased form 1.9% to 13.0% (24/153), although the number of gastric cancer patients treated by open laparotomy was decreased (58.9% 109/185). In Period III, the ratio of laparoscopic surgery (32.0% 49/153) was markedly increased compared to Periods I & II, while increase in the ratio of endoscopic treatment was limited (52/153 34.0%). because application of endoscopic treatment was limited to the gastric cancer within themucosa. This study clearly demonstrated therapeutic approach to the gastric cancer was replaced open laparotomy with endoscopic treatment and laparoscopic surgery in recent 10 years, although backgrounds of the gastric cancer were not changed.

Mo1553 Predictive Factors and the Frequency of Lymph Node Metastasis in Early Gastric Cancer

determined by a wound healing assay. In xenografted model (NCI-N87), mice were injected (SC; 200 ug/head, 10 mg/kg or IV; 300 ug/head, 15 mg/kg) with CP-RUNX (HM85R) for 3 weeks. This experiment showed that local or systemic delivery of CP-RUNX3 could significantly reduce tumor growth (p<0.05). p21Cip1/Waf1 and VEGF expression in lung and tumor were also significantly increased and decreased, respectively. Conclusion: These results suggest that In Vivo protein replacement therapy with cell-permeable and tissuedistributable recombinant proteins containing MTD can intervene in an abnormally active or dysfunctional intracellular process. Therefore, we conclude that intracellular delivery of RUNX3 with MTD could be useful for treating gastric cancer.